Endocrine Abstracts

Background: Soluble alpha klotho (sαKL) is a peptide hormone, that has been shown to be elevated in serum of patients with uncontrolled acromegaly. One early pilot study suggested that sαKL is also detectable in urine from patients with acromegaly, and significantly drops after surgery. Notably, in this study, urine sαKL concentrations were undetectable in the control group, and fell consistently below the detection limit of the ELISA in postoperative patients in the acromegaly group. We previously found considerable impact of various preanalytical conditions on measured concentrations of urine sαKL, pointing to the need to define an appropriate pre-analytical process.

Aim: In this study, we evaluated urine sαKL collected under standardized conditions as a potential biomarker in a cohort with patients with acromegaly receiving a variety of therapy modalities as well as a healthy cohort.

Methods: Blood and corresponding spontaneous urine samples were collected from biochemically uncontrolled (IGF-I >1.3 times upper limit of normal (×ULN); n=20) and controlled (IGF-I <1.0×ULN; n=31) patients with acromegaly as well as from healthy subjects (n=51); Patients had a variety of therapy modalities. Serum was stored at -20°C and urine at -80°C. Anthropometric data and routine lab values were collected. SαKL was measured with a sandwich ELISA (IBL, Hamburg, Germany).

Results: No meaningful correlation could be established between urine sαKL and serum sαKL, IGF-I × ULN, IGFBP 3 × ULN, eGFR nor urine creatinine. A strong correlation was shown for urine sαKL and urine pH (Spearman’s rho 0.770, P<0.001, n=101), with particularly low sαKL in samples with low pH. However, even after including only urine samples with pH greater or equal to 6.0, no correlation between the former mentioned parameters and urine sαKL was observed.

Conclusions: Interpretation of urine sαKL seems difficult at least. First, concentrations become very low or even undetectable in urine samples with a pH less than 6.0. Furthermore, even in samples with higher pH, concentrations of sαKL in urine do not correlate to serum concentrations. It is quite conceivable that additional factors impact urine sαKL concentration. Perhaps, more appropriate sampling conditions can be found. However, at present, our data do not support utilization of urine sαKL as a biomarker for growth hormone. In contrast, our data from this study further confirm serum sαKL correlates well with IGF-I.